Finally, our data demonstrate that single treatment of ALK-amplified NBs with either an ALK inhibitor or a p53 activator is insufficient to induce apoptosis, and that combination treatment with an ALK inhibitor and a p53 activator is required to overcome resistance to the ALK inhibitor and to suppress tumour relapse by activating the pro-apoptotic pathway as a result of SOX4-mediated PUMA upregulation (Supplementary Figure 7). This evidence concerns the gene ALK and neoplasm.